Neurokinin-1 Receptor and Its Signaling Components in Colitis-associated Dysplasia PROJECT LEADERS Leader: Caroline B. Appleyard, Ph.D. Ponce School of Medicine, Puerto Rico Co-Leader: Jie Wu, Ph.D. H. Lee Moffitt Cancer Center &Research Institute, Tampa, Florida ABSTRACT Colorectal cancer is one of the leading cancers in Puerto Rican, second only to prostate and breast cancer. Inflammatory bowel diseases such as ulcerative colitis and Crohn's disease have been linked to the development of colorectal cancer. Evidence obtained by us and others have suggested that substance P (SP) and its high affinity receptor neurokinin-1 receptor (NK-1R, tachykinin receptor 1) play a pivotal role in inflammatory bowel diseases. Both NK-1R and cyclooxygenase-2 (Cox-2) are upregulated in patients with inflammatory bowel diseases. However, the roles of NK-1 R-mediated signaling pathways in the pathogenesis of precancerous and cancerous lesions in ulcerative-associated colorectal cancer are not known. The longterm goals of this research project are to understand molecular mechanisms of ulcerative colitis-associated colorectal cancer and to target key signaling molecules in the development of ulcerative colitis-associated colorectal cancer for preventive and therapeutic intervention. The current study is designed to test the central hypothesis that NK-1R plays a key role in upregulation of Cox-2 in our rat model of colitis-associated dysplasia, and that the epidermal growth factor receptor (EGFR) and Src family tyrosine kinases (SFKs) are involved in NK-1R signaling in colon carcinoma cells, and in the development of precancerous lesions in this model of colitis-associated dysplasia. Three specific aims will be pursued in this collaborative research project that combines the strength of Dr. Appleyard in the rat model of ulcerative colitis-associated colorectal cancer and the expertise of Dr. Wu in growth factor receptor and G protein-coupled receptor (GPCR) signaling. In addition to giving novel insights into the roles of NK-1R and its mediators in the development of colorectal cancer, this collaborative research project will provide Dr. Appleyard with an excellent platform to strengthen her competitiveness in the areas of biochemical and molecular cancer research. This in turn will increase the likelihood for Dr. Appleyard in the Minority-Serving Institute (MSI) to successfully compete for a R01 grant from the National Cancer Institute (NCI) and will increase the quality of graduate education at the MSI. Title: Cutaneous human papillomavirus infection and non-melanoma skin cancer in the U.S. and Puerto Rico Project Leaders: Leader: Jaime Matta, Ph.D. Ponce School of Medicine (MSI) Co-Leader: Dana E. Rollison, Ph.D. H. Lee Moffitt Cancer Center &Research Institute (Cancer Center) Abstract: Non-melanoma skin cancer (NMSC), the most common cancer in U.S. men and women, is associated with increased risks of other cancers and high treatment costs at a national level. In addition to sun exposure and older age, immunosuppression is a risk factor for NMSC. Approximately 75% of NMSC's occurring in transplant patients contain human papillomavirus (HPV) DNA, suggesting that cutaneous HPV infection may be a cofactor in the etiology of NMSC among immunosuppressed individuals. Although prevalence estimates for HPV in NMSC tissues among immunocompetent individuals range from 35% to 45%, the role for HPV infection in the development of NMSC is unclear, since few seroepidemiologic have been published, most of which were conducted in predominately Caucasian populations with minimal sun exposure. Importantly, chronic sun exposure may affect cutaneous HPV infection, and HPV oncoproteins may promote progression of a pre-malignant lesion initiated by UV radiation. We propose to investigate circulating antibodies to cutaneous HPV types as a risk factor for non-melanoma skin cancer within two chronically sun-exposed populations of different ethnic compositions. Specifically, antibodies to cutaneous HPV types will be measured in 100 NMSC cases and 100 controls recruited from dermatologists'offices and health fairs in Puerto Rico, and in 100 NMSC cases and 100 controls identified from patients at the dermatology and skin screening clinics of the University of South Florida and H. Lee Moffitt Cancer Center &Research Institute (HLMCC) in Tampa, FL. The objectives of this 2-vear pilot study are to demonstrate the feasibility of data collection and to obtain estimates of HPV antibody prevalence in NMSC cases and controls from both populations to be used in sample size calculations for future grant applications. Additionally, potential interactions between HPV infection and known skin cancer risk factors, such as tanning ability and DNA repair capacity will be explored. The importance of conducting this pilot study within the context of these two populations must be emphasized, since both are chronically sun-exposed and ethnically diverse. The ultimate goal of this research is to further our understanding of the relationship between HPV and NMSC, so that additional prevention strategies for NMSC may be developed. Program 1: Title: Cancer Training and Education Program Co-Leaders; MCC/USF PSM Melissa Alsina, M.D. Jose A. Torres-Ruiz, Ph.D.. Scott Antonia, M.D., Ph. D Elizabeth Barranco, M.D. Daniel Sullivan, M.D. Kazim Husain, Ph.D. Kenneth Wrigth, Ph.D. Yasuhiro Yamamura, Ph.D. Kenira Thompson, Ph.D. Abstract: The main goal of this program is to develop a joint training program between the PSM and MCC/USF in order to enhance training and exposure of minority medical students and scientists to cancer research and subspecialized areas of oncology while educating majority trainees, physicians, and scientists to understand issues and problems associated to cancer disparities in minority populations. To achieve this goal we will pursue the following specific aims: 1. To develop training opportunities for medical students from PSM in cancer research and subspecialized areas of clinical oncology, and to develop training and education opportunities for medical students from USF in primary medicine in underserved and minority patient populations. 2. To establish a cooperative training program to promote PSM graduate students to pursue a career in cancer research and to facilitate greater awareness within the HLMCC Cancer Biology PhD program of the cancer issues important to the Hispanic population. 3. To develop investigator-initiated clinical research capability at the PSM and improve Hispanic participation in clinical trials at the MCC. Achievement of these objectives through this partnership will ultimately result in independent cancer research capability at the PSM, improve the effectiveness of the MCC in conducting activities specifically designed to address the cancer disparities in underserved Hispanic populations and establish a long term collaborative relationship between PSM and MCC in cancer research and training. Title: Outreach Efforts for the Partnership between H.L Moffitt Cancer Center and Ponce School of Medicine Names of Co-Leaders: Moffitt: Gwendolyn P. Quinn, Ph.D.;Clement Gwede, Susan Thomas Vadaparampil, Ph.D., MPH. Thomas H. Brandon, Ph.D.;Ponce: Marieva Puig, Ph.D., Julio Jimenez, MD, Vivian Green, LND, MS, Ph.D., Juan C. Orengo, MD, MPH,Ph.D. A. Abstract: The goal of the Outreach component of this project is to create a mutually beneficial planning partnership for developing culturally competent community outreach programs for cancer prevention and control for Puerto Ricans in the Island (Ponce Region) and those in the U.S. Mainland (Florida) using a social marketing modelr The initial phase of this collaboration aims to the establishment of efficient communication channels to share areas of expertise among institutions in order to develop culturally relevant cancer outreach programs for Puerto Ricans in the island and Mainland. Faculty from Ponce School of Medicine and H. Lee Moffitt Cancer Center and Research Institute will join community partners to assess community needs in the areas of cancer prevention and control. The information obtained from this community needs assessment will guide the development of culturally competent community based outreach programs in cancer education and prevention for Puerto Ricans. This project aims to provide opportunities for faculty development in the design and implementation of culturally appropriate outreach programs for Cancer prevention and control. A long-term goal is to foster the development of a collaborative team of investigators with expertise on conducting community outreach programs in cancer control and prevention among the Puerto Ricans living on the island and the Mainland.